The majority of Human immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) co-infected patients are non responders after 48 weeks of the current standard-of-care with Peg-Interferon/Ribavirin. The results of re-treatment are disappointing. The addition of Boceprevir to the current standard-of-care has been shown to increase the efficacy of therapy in HCV mono-infected patients previously treated with a bi-therapy. Knowing that HIV/HCV co-infected patients are subject to more rapid hepatic fibrosis as well as to increased risks of cirrhosis, end-stage liver disease and hepatocellular carcinoma, it is important to improve the response rate of the re-treatment of hepatitis C in these patients.

The aim of this pilot study is to evaluate the efficacy and safety of Boceprevir in combination with Peg-Interferon alfa 2b plus ribavirin, in patients co-infected with HIV and chronic genotype 1 HCV, and previously treated with Peg-Interferon/Ribavirin. 80 subjects will be enrolled. The primary endpoint will be the Sustained Virologic Response (SVR) defined as undetectable HCV-RNA at Week 24 after the end of therapy.

Pilot Study to Assess the Efficacy and Safety of Boceprevir, in Combination With Peg-Interferon Alfa and Ribavirin, in Patients With HCV/HIV Co-infection Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin

Pharmacokinetic parameters (Cres, Cmax, AUC) of anti-retroviral treatments before (baseline) and after (W8) the starting of Boceprevir combination in a sub-group of subjects and according to UGTA1 polymorphism.

Evaluation of Pharmacokinetic parameters (Cres, Cmax, AUC) of anti-retroviral treatments before (baseline) and after (W8) the starting of Boceprevir combination in a sub-group of subjects and according to UGTA1 polymorphism.

Area Under the Curve (AUC) of antiretrovirals [ Time Frame: Day 0 and W8 ] [ Designated as safety issue: No ]

Evaluation of pharmacokinetic parameters (Cres, Cmax, AUC) of anti-retroviral treatments before (baseline) and after (W8) the starting of Boceprevir combination in a sub-group of subjects and according to UGTA1 polymorphism.

If undetectable HCV RNA at W8, it is a complete virological response: 3 drug-regimen is continued until W48, then there is a follow-up period up to W72 and SVR analysis,

If HCV RNA ≤ 1000IU/mL at W8, it is an incomplete virological response. The 3-drug-regimen is continued until W72, when another analysis is done.

Other Names:

ViraferonPeg

Rebetol

Detailed Description:

The majority of HIV/HCV co-infected patients are non responders after 48 weeks of the current standard-of-care with Peg-Interferon/Ribavirin. The results of re-treatment are disappointing. The addition of Boceprevir to the current standard-of-care has been shown to increase the efficacy of therapy in HCV mono-infected patients previously treated with a bi-therapy. Knowing that HIV/HCV co-infected patients are subject to more rapid hepatic fibrosis as well as to increased risks of cirrhosis, end-stage liver disease and hepatocellular carcinoma, it is important to improve the response rate of the re-treatment of hepatitis C in these patients.

Subjects enrolled in this trial will have many predictive factors of failure: HIV co-infection, previous failure to Peg-Interferon/Ribavirin, HCV genotype 1 infection. One study reported a SVR rate of 9% after re-treatment with Peg-Interferon/Ribavirin in such patients. Another trial has shown a substantial increase of the response rate with a tri-therapy in HCV mono-infected patients.

The investigators propose to carry out a multicentric, national, non-randomized phase II trial in 80 patients.

The proportion of patients with F4 cirrhosis will have to be inferior to 50% of enrolled subjects.

The number of null responders to a previous treatment (HCV RNA drop < 2 log10 at W12) and without F4 cirrhosis will have to be lower or equal to 20.

The primary objective of the study is to estimate, in Genotype 1 - HCV/HIV co-infected patients, non responders to a previous therapy with Peg-Interferon/Ribavirin, the rate of SVR after 48 or 72 weeks of a three-drug regimen containing Peg-Interferon, Ribavirin and Boceprevir according to the Virologic Response and to compare the SVR rate to a threshold rate 20%, lowest rate to consider a therapeutic benefit in this population.

A pharmacokinetic sub-study including 30 patients will be performed to estimate pharmacokinetic parameters of antiretroviral treatment (Atazanavir combined with Ritonavir, Raltegravir, Tenofovir) in combination with anti HCV treatment at baseline and W8 and pharmacokinetic parameters of Boceprevir at W8.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Adult ≥18 years

HIV-1 infection

Infection to genotype 1 HCV only

Patients must have received at least 12 weeks of treatment with Peg-Interferon alfa 2a ≥ 135 µg / once weekly or Peg-Interferon alfa 2b ≥ 1,0 µg/kg/ once weekly + Ribavirin ≥ 600 mg daily and must have failed to treatment.

Anti-HCV treatment stopped for at least 6 months

Patients must be already treated at screen since at least 3 months with a stable combination of antiretroviral treatment as following:

Either tenofovir - emtricitabine, and atazanavir in combination with ritonavir

Or tenofovir - emtricitabine, and raltegravir

If patients cannot receive neither of the two antiretroviral regimens proposed, for virologic, safety or toxicity reasons, patients could receive any effective antiretroviral therapy including : tenofovir, emtricitabine, lamivudine, atazanavir alone or in combination with ritonavir, raltegravir, abacavir. These patients are not allowed to take part in the pharmacokinetic sub-study.

CD4 > 200/mm3 et >15%, at screen

HIV-RNA < 50 copies/ml since at least 6 months at screen

≥ 40 Kg and ≤ 125 Kg

Patients with any fibrosis grade. Proportion of F4 subjects should not excess 50% of the overall subjects.

Male and female subjects must agree to use acceptable methods of contraception 1 month prior to starting the study treatment and to continue until 7 months after the last doses of study drugs for male subjects and their partner(s), 4 months for female subjects.

Subjects must be willing to give written informed consent for principal study (signed at least at screen visit and prior to any study investigation)and + for the pharmacokinetic sub-study (for the concerned centers).

Subjects must be willing to give written informed consent for biological collection.

Subjects must be willing to give written informed consent for treatment of genetics data.

Subjects affiliated or beneficiary to a medical insurance.

Exclusion Criteria:

History:

Patients with cirrhosis (F4) and nul responders to prior treatment

Cirrhosis classified Child-Pugh B or C or history of decompensated cirrhosis of the liver. If Child A classification, significant varicose veins (grade 2 or 3) observed with a fibroscopy realized for < 3 years.

History of neoplasia within the last 5 years, except cutaneous basocellular carcinoma, recovering Kaposi's sarcoma, in situ cervical or anal canal cancer.

Current condition:

Co-infection with Hepatitis B virus

Pregnancy and lactation

Cardiac or severe pulmonary disease

Untreated dysthyroidism

Autoimmune disease contraindicating to an interferon treatment

Severe haemoglobinopathies

Any condition needing a systemic corticotherapy or an immunosuppressive treatment

Evolutive current malignancy, including hepatocarcinoma which should be specifically controlled prior to baseline.

Alcohol consumption which may disturb the study participation according to the investigator

Drug addiction which may disturb the study participation according to the investigator. Patients taking part to a substitution program with methadone or buprenorphine are allowed to be enrolled in the study.

History of discontinuation for intolerance to anti-HCV treatment.Patients with a history of discontinuation for intolerance, especially anaemia or leuconeutropenia, and who were not treated with hematopoietic growth factor, are eligible

Concomitant medication which may interfere with Boceprevir, atazanavir, ritonavir and raltegravir pharmacokinetic

St.John's-wort consumption

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01335529

Locations

France

CHU Sainte Marguerite

Marseille, France, 13009

Sponsors and Collaborators

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Rennes University Hospital

Merck Sharp & Dohme Corp.

Investigators

Principal Investigator:

Isabelle Poizot-Martin, MD

Marseille University Hospital

Study Chair:

Eric Bellissant, MD, PhD

Rennes University Hospital

More Information

No publications provided

Responsible Party:

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)